1. Field of the Invention
This invention relates to pharmaceutical preparations for parenteral use. More specifically, it relates to aqueous micellar solutions of the effective analgetic and antiemetic agents, levonantradol and N-methyllevonantradol, and to lyophile formulations of levonantradol and N-methyllevonantradol of improved stability which are of particular value for intramuscular administration of said analgetic agents.
2. Description of the Prior Art
Levonantradol, known chemically as [6S-[3S*,6-alpha,6a-alpha,9-alpha,10a-beta]]-5,6,6a,7,8,9,10,10a-octahydro -6-methyl-3-(1-methyl-4-phenylbutoxy)-1,9-phenanthridinediol 1-acetate, hydrochloride, and N-methyllevonantradol, the N-methyl derivative thereof, are effective analgetic and anti-emetic agents which are non-narcotic and free of addiction liability. Belgian Pat. No. 854,655, granted Nov. 16, 1977, describes the preparation and use of said compounds and their administration in composition form, said compositions including a pharmaceutical carrier selected on the basis of the chosen route of administration and standard pharmaceutical practice. Their administration in the form of tablets, pills, powders, capsules or granules containing excipients such as starch or milk sugar, or in the form of suspensions, solutions, emulsions, syrups and elixirs is also described therein.
Micellar solubilization of drugs which are insoluble in water or of low water solubility has been used to formulate clear aqueous solutions of such drugs. For example, incorporation of benzocaine into surfactant micelles to retard the rate of ester hydrolysis, and other pharmaceutical applications of micellar solubilization are described in Remington's Pharmaceutical Sciences, 15th Ed., Mack Publishing Company (1975), pages 283 and 320, respectively.